The status of the complement (C) system of gingival crevice fluid (GCF) from periodontal inflammatory lesions is compared with that of normal serum and of GCF from periodontal tissue with minimal inflammatory involvement. The cleavage of C3 and C5 serves as a parameter of C activation and possible inflammatory involvement. Comparisons are made between the cleavage patterns seen in C3 and C5 derived from GCF and those obtained with highly purified 125I trace labelled C3 and C5 incubated with GCF in vitro. A detailed physical-chemical analysis is performed by gel filtration, sucrose density gradient ultracentrifugation and by electrophoretic procedures. Highly specific antisera to C3, C5, lysosomal enzymes and to serum protease inhibitors help define immunochemically various C fragments as well as the enzymes causing C cleavage. The functional analysis employed in the definition of the C fragments include hemolytic, chemotactic and anaphylatoxic assays. The information gained by these studies may help us understand the involvement of C as a pathogenetic factor in periodontal disease.